Vitamin D

How is vitamin D made from non-dietary sources?

derived from cholesterol

synthesized from sun exposure

what are the two organs that make vitamin D happen (esp in form needs compounds)

liver and kidneys

every cell contains cholesterol. Skin cell produced from scratch through what compound?

7-dehydrocholesterol

cholesterol is found in every cell of our body - true or false?

true

what specific compound of cholesterol that exists in every skin cell?

7-dehydrocholesterol

when out in sun, and skin exposed. rays of sun UVB (beta rays) convert WHAT into WHAT?

7-dehydrocholesterol TO 7-precalciferol (pre vitamin D)

precalciferol thermalizes to produce what?

cholecalciferol

when we consume vitamin D what form?

animal source (3 oz salmon) - cholecalciferol D3

plant source (nuts, seeds, legumes, fungi) - ergocalciferol D2 (almost equivalent to cholecalciferol)

the skin cells can convert 7-dehydrocholesterol into what?

lumisterol

what does precalciferol convert to that does not produce vitamin D?

tachysterol

what product is needed to convert to active vitamin D?

cholecalciferol - through liver & kidney

UVB rays

• what sunscreen blocks

• prevents production of vitamin D (to become precalciferol)

ergocalciferol (plant sources)

D2 versus D3

D2 - plant origin (ergocalciferol)

D3 - animal origin (cholecalciferol)

D2/D3

D2 is almost equivalent in bioavailability to D3. When prescribed, D2 is often what prescribed, and cheaper too. 

UVB are not the only rays. Other types?

• tanning

• some compounds formed include l

• other UV rays

how much approximately of absorption?

50% of vitamin D

where is absorption HIGHEST?

duodenum/jejunum

Most absorption happens where?

distal SI

this is a fat soluble vitamin, so it is going to be what?

• incorporated into chylomicrons

• transported through lymph

• before going to throracic duct, subclavin vein, then liver. 

what protein is going to pick up vitamin D?

DBP - vitamin D binding protein (transcalciferin)

transcalfierin

name of vitmain D binding protein

storage?

inactive form in adipose tissue. some go in liver for conversion.

FAT STORAGE - VITAMIN D is STORED (Cholecalciferol).

more fat stored, concentrations of active forms of vitamin D are what?

lower.

obese/overweight: lower vit D levels because storage capacity is graeter, but concentrations in blood are lower.

if coming from skin, does it go through GI?

no. diffused INTO BLOOD. Picked up by hepative vitamin D binding protein (DBP)

skin → liver

vitamin DBP (go to liver)

in blood, how transported?

bound to vitamin DBP. 60% others albumin, lippoprteins, or globulins. m

metabolized?

cholecalciferol into active form

levels of metabolism

1) liver 2) kidney

Metabolism

enzyme: 25 hydroxylase (LIVER) - NADPH dependent & mitochondrial enzyme

cholecalciferol → 25-OH D

**(no subscript because happen to D2 plant and D3 skin/animal)

what is the normal serum concentration of blood?

30-40 ng/mL

in 1 mL of blood, 30-40ng of vitamin D

why importantn to know serum levels?

consumer - need to know if need supplementation or not

After 25-OH D leaves liver, taken up by the kidneys. What happens in kidneys?

ENZYME: 1-alpha-hydroxylase - NADPH dependent

PRODUCES 1,25-OH D

(choleclafierol) → caldiol (25-OHD) → CAlcitriol (1,25-OH D)

is this enzyme (1-alpha-hydroxylase) present outside the kidney?

bone, skin, intestines

which mineral is acted upon vitamin D?

calcium

from the bone, important factor that bone produces that signals vitamin D enzyme in kidney to convert to 1,25 OH D. what is it?

FGF - fibroblast growth factor

FGF 23 (most predominant)

in the kidneys, 25-OH-D and DBP bind to what?

cubulin-megalin membrane complex

the cubulin-megalin compelx is internalized through what?

endocytosis.

Liver produces what? Kidney produces what?

liver: 25-OH (calcdiol)

kidney: 1,25 OH & 24,25 OH

why does kidney convert to 24,25 OH

if plenty of 1,25 OH in kidney, converts to 24,25 OH

why 24,25 OH produced?

levels of active vitamin D is HIGH. supress 1-alpha-hydroxylase. Increase 24-hydroxylase. 

if 1,25 OH levels are not high, can still kick up 24-hydroxylase. Converts to what?

1,24,25 OH3 D

which one is measured?

25-OH

what is the half life of 1.25 (OH)2

short: 2-6 hours. not a good representation of time measure. which is why not assessed (active form).

range of 20-40 picograms/dL. This is a tiny fish in a LARGE OCEAN. need higher precision to quantify.

where does activation of vit D happen?

liver and kidneys

where vit D stored?

liver and fat

why vit D pushed to get activated?

calcium inadequacy and homesostatis.

calcium levels are down?

PTH homrone produces to increase calcium levels. 

when calcium is up? produce what hormone?

calcitonin

3 horseman:

PTH, calcitationin, vit D

excretion of vit D?

bile. richest presence of vit D receptors in intestines.

activated vit D (1,25 OH2) targets a nuclear receptor?

VDR: vitamin D receptor. VDRE (response element is the segment of machinery genomic. forms a complex). 

binding and RE - affect transcription gene

Remember: vit A targets RXR and RAR. RARE (response element)

action of vit D - interacts with 2 CALCIUM BINDING PROTEINS. from genetic machinery, synthesizes the 2 calcium binding proteins. 

calbidin: INTESTINAL calcium binding protein

calmodulin: INTERCELLULAR (within cells) calcium binding proteins (not intestinal, general, found in every single cell)

vit D in diet

bring calcium in food (diet or supplement), transport into intestinal cell. to absorb calcium.

calbindin

calcium binding protein in the BRUSH BORDER of the intestine

in intestinal cell, vitamin D through genoic machinery causes production of CALBINDIN. pushes to brush border. CALBIDIN facilitates thru calcium channel protein to increase calcium. 

Non-Genomic Action of (1,25 OH2 D)

intracellular SIGNALING. BETWEEN cells and tissues.

• uptake of calcium in tissue.

• movement of calcium between tissues.

• influencing concentrations in tissues (fat, bone, intestinal cells).

Optaiml Serum Ca level

8.5-10.5mg/dL

IDEAL: 10-10.5 (higher end)

how influence Ca levels?

• VDRE: increase Ca in intestine (Calbindin)

• Reabsorption from kidneys. kidney filter blood. kidney can let calcium go. kidney get rid of calcium. Sodium helps

• Ca resorption of bone. Calcium in bone. pulled from storage. structurally important in bone. 

PTH

activate vit D

stop Kidney letting go od calcium

still need Ca: push ca from bone

when Calcium levels are LOW

• Less than 8.5mg/dL

• PTH: senses low blood calcium, triggers Parathyroid hormone release

• 2 Actions: 1) high PTH causes Kidney to increase 1-alpha-hydroxylase (produces 1,25OH D - the active form of vit D). 2) kidney filters blood and minerals. PTH tells kidneys NOT to get rid of calcium. REABSORB calcium, decrease excreiton of calcium. not going to bring up, prevent calcium levels from getting lower.

• what is role of vit D? increase calcium absorption. calcium is absorbed in the intestine. increases calbidin (calcium binding protein) → increase calcium absorbed in the intestine. 

• in the end? no calcium in the diet/gut, and kidney did work? BONE → resorption. Calcium is stored in bone (hard tissue). MOBILIZING (pulling out).

what is something that active vit D does that PTH does not do?

increases Ca absorption

When Ca is HIGH…

• thyroid releases calcitonin

• opposite effects of above. 

• want to put calcium back to bone. it is HARDER to build. not easy to build boner. easier to destroy. 

• our bone mass, and peak bone mass has already occured. dont have growth plates to build bone. 

• NO vit D activation, no calbidin trigger

• which enzymes shut down? NO active D 

• kidney produces 24 hydroxylase (so instead of being convert to 1,25 OH, converts to 24,25 OH which is not the active form)!!!!

• PTH gland active?

calcitonin what does it act?

bones!!

when high, PTH FALLS - cause kidneys to turn away from 1-alpha hydroxylase to turn in 24 hydroxylase. CALCITONIN does not trigger. PTH suppressed does this. 

PTH acted on what?

kidneys & vit D

how is calcium stored in bone?

Ca + P → super satured solution called hydroxyappetite.

what does the combination of protein matrix, bone tissue give?

tensile strength to withstand force

2 types of bone cells

osteoblasts and osteoclasts

osteoclasts

bone resorbing cells

mobilize Ca and P from bone (release both - hydroxyapetitie)

sercete acid to digest proteins structure, pits

osteoblasts

laye down mineral/matrix. other minerals are stored in bone.

other functions of Vitamin D?

• similar to vit A

• VDR: affects cell growth, cycle, diffentiation

• vit D protect from cancers (breast, colon, prostate) and increase apoptosis.

• research in 24,25 and (1,24,25 OH)

• linked to blood presure rgulation, aiutomimmune, obesity. 

vit D deficiency

causes hypocalcemia - low blood levels of calcium.

other s/s: seizures, tetany (muscles cells firing), sometimes death. 

those who live in northern climates and indoors - risk of deficiency

2 diff types of rickets:

1) Type 1 - KIDNEY ENZYME DEFECTIVE. vit D not produce bc kidney doesn’t supply 1,25 OH

2) Type 2 - RECEPTOR for 1,25 OH is NOT PRESENT. vit D cannot bind to receptors in intestine, kidney, and bone. 

interactions with vit D

Ca, P,

vit K - can include transport vit D

calcitroic acid

excreted through urine

vit D & vit E

multiply ug x 40 = IU

conversion factor of 40